Motonobu Nakamura

Expression of toll-like receptor 2, NOD2 and dectin-1 and stimulatory effects of their ligands and histamine in normal human keratinocytes

Background  Epidermal keratinocytes are involved in the skin innate immunity and express toll‐like receptors (TLRs) and other innate immune proteins. The epidermis is continuously exposed to pathogenic Gram‐positive bacteria or fungi. However, few studies have examined the function and expression of innate immune proteins in keratinocytes. Histamine, which is well known for itch and allergy, is closely associated with innate immunity, but its influence on epidermal innate immunity is still unclear.

Downmodulatory Effects of the Antihistaminic Drug Bepotastine on Cytokine/Chemokine Production and CD54 Expression in Human Keratinocytes

Bepotastine besilate is an antihistaminic drug of the second generation with superior clinical responses. In this study, we investigated whether bepotastine modulates the production of cytokines/chemokines and the expression of CD54 in human epidermal keratinocytes. The production of IL-1α, CXCL10, and CCL17 and the expression of CD54 were significantly suppressed by the addition of bepotastine. Bepotastine exerts its antiallergic action on keratinocytes by suppressing the production of certain proinflammatory cytokines, both Th1 and Th2 chemokines, and possibly by inhibiting the expression of CD54.

Effects of oral antibiotic roxithromycin on quality of life in acne patients

Macrolides are effective for inflammatory acne, but there are not many studies on roxithromycin. In this study, patients with acne were surveyed for improvement of their quality of life after treatment with roxithromycin. Patients were orally given roxithromycin 300 mg daily for 2–4 weeks. At the time of pre‐ and post‐treatment, the dermatologists graded the severity of acne symptoms, and the patients answered questionnaires. In 123 half faces of 76 patients, 80 half faces were improved, 42 half faces were not changed, and one half face was deteriorated. The score of “symptom and feeling” and “leisure” in DLQI‐J and “emotions” and “symptoms” in Skindex‐29‐J were significantly decreased after roxithromycin treatment. Roxithromycin has a therapeutic effect on inflammatory acne and leads to improvement of quality of life in the patients.

Epidermolysis Bullosa Acquisita Associated with Psoriasis

Journal Compilation

Acute onset disseminated superficial porokeratosis associated with exacerbation of diabetes mellitus due to development of anti-insulin antibodies

The development of disseminated superficial porokeratosis is occasionally observed in association with renal transplant, autoimmune diseases, and various hematological disorders, suggesting a certain immunosuppression may trigger a wide-spread abnormal keratinization. Here we report a case of sudden onset disseminated superficial porokeratosis associated with an exacerbation of diabetes mellitus due to an anti-insulin antibody formation. To our knowledge, this is the first report of disseminated superficial porokeratosis in a patient with severe diabetes mellitus.

Calcinosis cutis associated with primary Sjögren's syndrome: strong expression of osteonectin and matrix Gla protein

plementation as maintenance therapy for osteoporosis. Within a month the painful swelling of the left foot disappeared completely. In April 2010 the patient suddenly complained of tender swelling at the anterior left side of the base of the neck, without fever. On examination, we found tenderness and swelling of the left sterno-clavicular joint associated with normal body temperature. The anterior radionuclide bone scan showed a hot spot on the same anatomical site, consistent with arthritis. Compared with the values found in 2006, the bone densitometry (lumbar along with femoral sites) revealed increased levels of BMD. The patient received a single IA injection of triamcinolone acetonide, 40 mg. Pain and joint swelling markedly improved, with almost complete recovery of the articular function. Two months later, symptoms relapsed. Physical examination, once again, confirmed a painful swelling over the left upper angle of the sternum, suggestive of joint effusion in the sterno-clavicular joint. The CT scan (Fig. 1) revealed chondrocalcinosis of sterno-clavicular joints bilaterally. Due to its uncommon occurrence, the real nature of sterno-clavicular arthritis is often hard to establish. In daily rheumatological practice, frequent causes of sterno-clavicular inflammation are sero-negative SpAs. Among them, SAPHO syndrome shows relevant predilection for those peculiar joints. Altered inflammatory markers along with fever are indicative of septic arthritis, whereas elderly onset should suggest degenerative or metabolic diseases such as chondrocalcinosis. In summary, this patient displayed pseudogout attacks in the left sternoclavicular joint due to an uncommon localization of calcium pyrophosphate dihydrate disease [1].

Congenital woolly hair without P2RY5 mutation

Congenital woolly hair is a disorder with structural defects of the hair shafts. Curled hairs are noticed at birth or soon after birth and often improve with age. Some cases of woolly hairs are associated with systemic or other skin diseases. Congenital woolly hair without any associated disorder is inherited in an autosomal dominant or autosomal recessive manner. Recently, mutations in P2RY5 gene, encoding a G-protein coupled receptor, have been shown to be responsible for autosomal recessive woolly hair. Here, we report the second Japanese case of congenital woolly hair, showing no P2RY5 gene mutation.

CD30-positive Cutaneous Pseudolymphoma Caused by Tocilizumab in a Patient with Rheumatoid Arthritis: Case Report and Literature Review

Tocilizumab is a biological disease-modifying anti-rheumatic drug (DMARD) that targets interleukin 6 (IL-6) receptor, blocking IL-6 signalling (1). Tocilizumab has shown efficacy in the treatment of rheumatoid arthritis (2); however, it sometimes induces cutaneous adverse reactions. We report here a case of pseudolymphoma caused by tocilizumab, manifesting as an unusual cutaneous eruption. We also review the literature concerning drug eruption caused by tocilizumab, and pseudolymphoma caused by biologics in general.

Photoallergic Drug Eruption Caused by Certolizumab Pegol.

Certolizumab pegol is a novel tumour necrosis factor (TNF) inhibitor, comprising a humanized Fab antigenbinding fragment fused to a 40-kDa polyethylene glycol (PEG) moiety (1). This unique structure avoids the potential Fc-mediated effects seen in vitro, such as complement-dependent or antibody-dependent cellmediated cytotoxicity or apoptosis (2). Certolizumab pegol is used to treat autoimmune diseases, such as Crohn’s disease and rheumatoid arthritis, and exhibits strong anti-inflammatory effects. Although diarrhoea and vomiting have been reported as adverse events of treatment with certolizumab pegol, there have been few case reports of cutaneous side-effects, such as psoriasiform drug eruption (3). We report here the first case of photoallergy caused by certolizumab pegol.

Tuberculosis verrucosa cutis with elevation of circulating T-helper 1 and 17 cells and their reductions after successful treatment

1 Kanitakis J, Audeffray D, Claudy A. Squamous cell carcinoma of the skin complicating lupus vulgaris. J Eur Acad Dermatol Venereol 2006; 20: 114–116. 2 Yeager J, Findlay R, McAleer I. Penile verrucous carcinoma. Arch Dermatol 1990; 126: 1208–1210. 3 Noel JC, Heenen M, Peny MO et al. Proliferating cell nuclear antigen distribution in verrucous carcinoma of the skin. Br J Dermatol 1995; 133: 868–873. 4 Noel JC, Peny MO, De Dobbeleer G et al. p53 protein overexpression in verrucous carcinoma of the skin. Dermatology 1996; 192: 12– 15. 5 Noel JC, Fayt I, De Dobbeleer G, Simonart T. Pattern of MIB-1 distribution in cutaneous verrucous carcinoma: analysis of 5 cases (abstract). J Invest Dermatol 2002; 118: 907. 6 Harrison PV, Marks JM. Lupus vulgaris and cutaneous lymphoma. Clin Exp Dermatol 1980; 5: 73–77. 7 Sowden J, Paramsothy Y, Smith AG. Malignant melanoma arising in the scar of lupus vulgaris and response to treatment with topical azelaic acid. Clin Exp Dermatol 1988; 13: 353–356. 8 Assaf C, Steinhoff M, Petrov I et al. Verrucous carcinoma of the axilla: case report and review. J Cutan Pathol 2004; 31: 199–204. 9 Noel JC, Peny MO, Detremmerie O et al. Demonstration of human papillomavirus type 2 in a verrucous carcinoma of the foot. Dermatology 1993; 187: 58–61. 10 Pattee SF, Bordeaux J, Mahalingam M, Nitzan YB, Maloney ME. Verrucous carcinoma of the scalp. J Am Acad Dermatol 2007; 56: 506–507.